Abstract This is an application for a Diversity Supplement to support Brandon Young, who is a PhD student in the laboratory of Christopher Davies, PhD, at the Medical University of South Carolina. Mr. Young is an African-American who seeks a career as an independent academic investigator working as a structural biologist in an area of public health need. The overall goals of the parent R01 (NIGMS GM066861) are to investigate the molecular mechanism of cephalosporin resistance in N. gonorrhoeae conferred by mosaic penA, which encodes penicillin-binding protein 2 (PBP2). To support the training of Mr. Young, we have developed two aims that extend and complement those of the parent R01. The first aim is to elucidate the molecular mechanism of penA mutations that confer cephalosporin-resistant in a new strain of N. gonorrhoeae that emerged very recently in Canada. The second aim is to develop Structure- Activity Relationships of a panel of cephalosporins against PBP2 variants and N. gonorrhoeae strains with the goal of (a) identifying existing cephalosporins that might have value as antigonococcal agents and (b) suggesting new synthetic routes toward replacement cephalosporins. This research program will provide Mr. Young with extensive training in structural and biophysical techniques (X-ray crystallography, NMR spectroscopy, isothermal titration calorimetry & fluorescence spectroscopy), while learning about protein structure, antibiotic resistance, drug discovery, and microbiology and biochemistry in general. Alongside, he will receive comprehensive training and mentoring so that he emerges well-equipped with the skills and knowledge necessary to embark on his chosen career.